tbuckley/cabot-search huggingface dataset:
Comparison of US Hospital Charity Care Policies Before vs After Onset of the COVID-19 Pandemic
Authors: Christopher Goodman, Amber Flanigan, Janice C. Probst, Ge Bai
Journal: JAMA Network Open (2022)

Tax-exempt hospitals are required to provide charity care to maintain their tax-exempt status; charity care policies must be published online with clear eligibility criteria. Prior research has shown wide variability in charity care policy content; it is unknown how hospitals change their charity care policies over time.To examine changes to tax-exempt hospital charity care policies before vs after the COVID-19 pandemic.This cohort study used downloaded charity care policies from a geographically representative sample of 170 tax-exempt hospitals from December 1 to 31, 2019, and December 1 to 31, 2021, and categorized the policy changes made as more restrictive, more generous, indeterminate, minimal, or not updated.Onset of the COVID-19 pandemic.The primary outcome was charity care policy content changes from 2019 to 2021. Also examined were the effects of hospital ownership type, state Medicaid expansion status, and hospital consolidation on policy changes.In this sample of 170 hospitals, 151 published documents available for comparison. Among these hospitals, 127 (84.1%) updated their charity care policies and 77 (51.0%) made substantial changes, with 242 distinct policy changes to categories such as income eligibility cutoffs, asset limitations, and service exclusions. Although the majority of hospitals expanded charity care (47 [31.1%]), a sizable minority restricted charity care (12 [7.9%]). Medicaid expansion during the study period and hospital consolidations were not associated with expansion of charity care; the largest merger in this sample led to reduced charity care at all 4 hospitals involved.Tax-exempt hospitals appear to have updated their policies with mostly positive changes during and after the onset of the COVID-19 pandemic; however, some hospitals restricted charity care in 2021 documents. Unpublicized or vague eligibility criteria may limit patients' understanding of charity care policies and conceal the full extent of charity care policy changes over time. Policy makers should consider requiring greater transparency and simplification for hospital charity care policies to ensure adequate access to care for uninsured and underinsured patients.
BMPR1A promotes ID2–ZEB1 interaction to suppress excessive endothelial to mesenchymal transition
Authors: Heon-Woo Lee, Takaomi Adachi, Boryeong Pak, Saejeong Park, Xiaoyue Hu, Woosoung Choi, Piotr S Kowalski, C Hong Chang, Katharine R Clapham, Aram Lee, Irinna Papangeli, Jongmin Kim, Orjin Han, Jihwan Park, Daniel G Anderson, Michael Simons, Suk-Won Jin, Hyung J Chun
Journal: Cardiovascular Research (2022)

Abstract Aims Components of bone morphogenetic protein (BMP) signalling have been implicated in both pathogenesis of pulmonary arterial hypertension (PAH) and endothelial-mesenchymal transition (EndoMT). In particular, the importance of BMP type 2 receptor in these processes has been extensively analysed. However, the contribution of BMP type 1 receptors (BMPR1s) to the onset of PAH and EndoMT remains poorly understood. BMPR1A, one of BMPR1s, was recently implicated in the pathogenesis of PAH, and was found to be down-regulated in the lungs of PAH patients, neither the downstream mechanism nor its contribution to EndoMT has been described. Therefore, we aim to delineate the role of endothelial BMPR1A in modulating EndoMT and pathogenesis of PAH. Methods and results We find that BMPR1A knockdown in endothelial cells (ECs) induces hallmarks of EndoMT, and deletion of endothelial Bmpr1a in adult mice (Bmpr1aiECKO) leads to development of PAH-like symptoms due to excessive EndoMT. By lineage tracing, we show that endothelial-derived smooth muscle cells are increased in endothelial Bmpr1a-deleted mice. Mechanistically, we identify ZEB1 as a primary target for BMPR1A in this setting; upon BMPR1A activation, ID2 physically interacts and sequesters ZEB1 to attenuate transcription of Tgfbr2, which in turn lowers the responses of ECs towards transforming growth factor beta (TGFβ) stimulation and prevents excessive EndoMT. In Bmpr1aiECKO mice, administering endothelial targeting lipid nanoparticles containing siRNA against Tgfbr2 effectively ameliorate PAH, reiterating the importance of BMPR1A-ID2/ZEB1-TGFBR2 axis in modulating progression of EndoMT and pathogenesis of PAH. Conclusions We demonstrate that BMPR1A is key to maintain endothelial identity and to prevent excessive EndoMT. We identify BMPR1A-induced interaction between ID2 and ZEB1 is the key regulatory step for onset of EndoMT and pathogenesis of PAH. Our findings indicate that BMPR1A-ID2/ZEB1-TGFBR2 signalling axis could serve as a potential novel therapeutic target for PAH and other EndoMT-related vascular disorders.
Augmenting randomized clinical trial data with historical control data: Precision medicine applications
Authors: Boris Freidlin, Edward L Korn
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract As precision medicine becomes more precise, the sizes of the molecularly targeted subpopulations become increasingly smaller. This can make it challenging to conduct randomized clinical trials of the targeted therapies in a timely manner. To help with this problem of a small patient subpopulation, a study design that is frequently proposed is to conduct a small randomized clinical trial (RCT) with the intent of augmenting the RCT control arm data with historical data from a set of patients who have received the control treatment outside the RCT (historical control data). In particular, strategies have been developed that compare the treatment outcomes across the cohorts of patients treated with the standard (control) treatment to guide the use of the historical data in the analysis; this can lessen the potential well-known biases of using historical controls without any randomization. Using some simple examples and completed studies, we demonstrate in this commentary that these strategies are unlikely to be useful in precision medicine applications.
The Laugh
Authors: Eunice Cho
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Critical Need to Modernize Syphilis Screening
Authors: Susan Tuddenham, Khalil G. Ghanem
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade
Authors: Varintra E. Lander, Jad I. Belle, Natalie L. Kingston, John M. Herndon, Graham D. Hogg, Xiuting Liu, Liang-I Kang, Brett L. Knolhoff, Savannah J. Bogner, John M. Baer, Chong Zuo, Nicholas C. Borcherding, Daniel P. Lander, Cedric Mpoy, Jalen Scott, Michael Zahner, Buck E. Rogers, Julie K. Schwarz, Hyun Kim, David G. DeNardo
Journal: Cancer Discovery (2022)

Abstract The effects of radiotherapy (RT) on tumor immunity in pancreatic ductal adenocarcinoma (PDAC) are not well understood. To better understand if RT can prime antigen-specific T-cell responses, we analyzed human PDAC tissues and mouse models. In both settings, there was little evidence of RT-induced T-cell priming. Using in vitro systems, we found that tumor–stromal components, including fibroblasts and collagen, cooperate to blunt RT efficacy and impair RT-induced interferon signaling. Focal adhesion kinase (FAK) inhibition rescued RT efficacy in vitro and in vivo, leading to tumor regression, T-cell priming, and enhanced long-term survival in PDAC mouse models. Based on these data, we initiated a clinical trial of defactinib in combination with stereotactic body RT in patients with PDAC (NCT04331041). Analysis of PDAC tissues from these patients showed stromal reprogramming mirroring our findings in genetically engineered mouse models. Finally, the addition of checkpoint immunotherapy to RT and FAK inhibition in animal models led to complete tumor regression and long-term survival. Significance: Checkpoint immunotherapeutics have not been effective in PDAC, even when combined with RT. One possible explanation is that RT fails to prime T-cell responses in PDAC. Here, we show that FAK inhibition allows RT to prime tumor immunity and unlock responsiveness to checkpoint immunotherapy. This article is highlighted in the In This Issue feature, p. 2711
Serplulimab With Chemotherapy in Extensive-Stage SCLC
Authors: Noura J. Choudhury, Gregory J. Riely
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Resurgence of Syphilis in the US—USPSTF Reaffirms Screening Guidelines
Authors: Erin H. Amerson, Herbert B. Castillo Valladares, Kieron S. Leslie
Journal: JAMA Dermatology (2022)

US Preventive Services Task Force; Carol M. Mangione, MD, MSPH; Michael J. Barry, MD; Wanda K. Nicholson, MD, MPH, MBA; Michael Cabana, MD, MA, MPH; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Carlos Roberto Jaén, MD, PhD, MS; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; John M. Ruiz, PhD; James Stevermer, MD, MSPH; John B. Wong, MD
Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention
Authors: Kuo-Wei Huang, Chih-Wei Chen, James Cheng-Chung Wei
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
IKappa <scp>B‐Kliev‐ε</scp> That the Inhibitor of <scp>NF‐κB</scp> Kinase Subunit ε (<scp>IKBKε</scp>) May Hold the Key to Treating <scp>NPSLE</scp>!
Authors: Carla M. Cuda
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
<i>Faecalibacterium prausnitzii</i> Attenuates CKD via Butyrate-Renal GPR43 Axis
Authors: Hong-Bao Li, Meng-Lu Xu, Xu-Dong Xu, Yu-Yan Tang, Hong-Li Jiang, Lu Li, Wen-Jie Xia, Nan Cui, Juan Bai, Zhi-Ming Dai, Bei Han, Ying Li, Bo Peng, Yuan-Yuan Dong, Sachin Aryal, Ishan Manandhar, Mahmoud Ali Eladawi, Rammohan Shukla, Yu-Ming Kang, Bina Joe, Tao Yang
Journal: Circulation Research (2022)

Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown.We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes.We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43.Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.
Serologic Profiling Using an Epstein-Barr Virus Mammalian Expression Library Identifies EBNA1 IgA as a Prediagnostic Marker for Nasopharyngeal Carcinoma
Authors: Sarita Paudel, Benjamin E. Warner, Renwei Wang, Jennifer Adams-Haduch, Alex S. Reznik, Jason Dou, Yufei Huang, Yu-Tang Gao, Woon-Puay Koh, Alan Bäckerholm, Jian-Min Yuan, Kathy H.Y. Shair
Journal: Clinical Cancer Research (2022)

The favorable prognosis of stage I and II nasopharyngeal carcinoma (NPC) has motivated a search for biomarkers for the early detection and risk assessment of Epstein-Barr virus (EBV)-associated NPC. Although EBV seropositivity is ubiquitous among adults, a spike in antibodies against select EBV proteins is a harbinger of NPC. A serologic survey would likely reveal which EBV antibodies could discriminate those at risk of developing NPC.Lysates from a new EBV mammalian expression library were used in a denaturing multiplex immunoblot assay to survey antibodies against EBV in sera collected from healthy individuals who later developed NPC (incident cases) in a prospective cohort from Singapore and validated in an independent cohort from Shanghai, P.R. China.We show that IgA against EBV nuclear antigen 1 (EBNA1) discriminated incident NPC cases from matched controls with 100% sensitivity and 100% specificity up to 4 years before diagnosis in both Singapore and Shanghai cohorts. Incident NPC cases had a greater IgG repertoire against lytic-classified EBV proteins, and the assortment of IgA against EBV proteins detected by the immunoblot assay increased closer to diagnosis.Although NPC tumors consistently harbor latent EBV, the observed heightened systemic and mucosal immunity against lytic-classified antigens years prior to clinical diagnosis is consistent with enhanced lytic transcription. We conclude that an expanding EBV mucosal reservoir (which can be latent and/or lytic) is a risk factor for NPC. This presents an opportunity to identify those at risk of developing NPC using IgA against EBNA1 as a biomarker.
Comparison of outcomes for HLA-matched sibling and haplo-identical donors in Myelodysplastic syndromes: report from the chronic malignancies working party of EBMT
Authors: Kavita Raj, Dirk-Jan Eikema, Vipul Sheth, Linda Koster, Liesbeth C. de Wreede, Didier Blaise, Carmela Di Grazia, Yener Koc, Victoria Potter, Patrice Chevallier, Lucia Lopez- Corral, Depei Wu, Stephan Mielke, Johan Maertens, Ellen Meijer, Anne Huynh, Jakob Passweg, Thomas Luft, Jose Antonio Pérez-Simón, Fabio Ciceri, Agnieszka Piekarska, G. Hayri Ozsan, Nicolaus Kröger, Marie Robin, Ibrahim Yakoub-Agha
Journal: Blood Cancer Journal (2022)

Myelodysplastic syndromes (MDS) are the second common indication for an Allo-HCT. We compared the outcomes of 1414 matched sibling (MSD) with 415 haplo-identical donors (HD) transplanted with post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis between 2014 and 2017. The median age at transplant with MSD was 58 and 61 years for HD. The median time to neutrophil engraftment was longer for HD being 20 vs 16 days for MSD (p < 0.001). Two-year overall survival (OS) and PFS (progression free survival) with MSD were significantly better at 58% compared with 50%, p ≤ 0.001, and 51% vs 47%, p = 0.029, with a HD. Relapse at 2 years was lower with a HD 23% than with MSD 29% (p = 0.016). Non relapse mortality (NRM) was higher with HD in the first 6 months post-transplant [HR 2.59 (1.5-4.48) p < 0.001] and was also higher at 2 years being 30% for HD and 20% for MSD, p ≤ 0.001. The incidence of acute GVHD grade II-IV and III-IV at 100 days was comparable for MSD and HD, however, chronic GVHD at 2 years was significantly higher with MSD being 44% vs 32% for HD (p < 0.001). After multivariable analysis, OS and primary graft failure were significantly worse for HD particularly before 6 months [HR 1.93(1.24-3.0)], and HR [3.5(1.5-8.1)]. The median age of HD 37 (IQR 30-47) years was significantly lower than sibling donors 56 (IQR 49-62 years) p < 0.001. However, there was no effect on NRM, relapse or PFS. This data set suggests that a MSD donor remains the preferred choice in MDS over a haplo donor. Transplants with haploidentical donors result in satisfactory long-term outcome, justifying it's use when no better donor is available.
Association of ultra-processed food consumption with colorectal cancer risk among men and women: results from three prospective US cohort studies
Authors: Lu Wang, Mengxi Du, Kai Wang, Neha Khandpur, Sinara Laurini Rossato, Jean-Philippe Drouin-Chartier, Euridice Martínez Steele, Edward Giovannucci, Mingyang Song, Fang Fang Zhang
Journal: BMJ (2022)

To examine the association between consumption of ultra-processed foods and risk of colorectal cancer among men and women from three large prospective cohorts.
Correction: Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial
Authors: Venkatraman Radhakrishnan, Sameer Bakhshi, Smita Kayal, Cherian Thampy, Ankit Batra, Praveen Kumar Shenoy, Hemanth Kumar, Swaminathan Rajaraman, Shilpi Chaudhary, Reema Bisht, Biswajit Dubashi, Trivadi S. Ganesan
Journal: Blood Cancer Journal (2022)
Machine learning for determining lateral flow device results for testing of SARS-CoV-2 infection in asymptomatic populations
Authors: Andrew D. Beggs, Camila C.S. Caiado, Mark Branigan, Paul Lewis-Borman, Nishali Patel, Tom Fowler, Anna Dijkstra, Piotr Chudzik, Paria Yousefi, Avelino Javer, Bram Van Meurs, Lionel Tarassenko, Benjamin Irving, Celina Whalley, Neeraj Lal, Helen Robbins, Elaine Leung, Lennard Lee, Robert Banathy
Journal: Cell Reports Medicine (2022)

Rapid antigen tests in the form of lateral flow devices (LFDs) allow testing of a large population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To reduce the variability in device interpretation, we show the design and testing of an artifical intelligence (AI) algorithm based on machine learning. The machine learning (ML) algorithm is trained on a combination of artificially hybridized LFDs and LFD data linked to quantitative real-time PCR results. Participants are recruited from assisted test sites (ATSs) and health care workers undertaking self-testing, and images are analyzed using the ML algorithm. A panel of trained clinicians is used to resolve discrepancies. In total, 115,316 images are returned. In the ATS substudy, sensitivity increased from 92.08% to 97.6% and specificity from 99.85% to 99.99%. In the self-read substudy, sensitivity increased from 16.00% to 100% and specificity from 99.15% to 99.40%. An ML-based classifier of LFD results outperforms human reads in assisted testing sites and self-reading.